Phthalazine amide

In this section, the general term phthalazine amides is used to cover phthala-zinecarboxamides, phthalazinecarbohydrazides, and their thio analogs. 

Dihydralazine (67-3) is the less important of the two phthalazine antihypetensive agents its preparation is however recorded first because of its simplicity. Thus, reaction of phthaUiydrazide (67-1) with phosphorus oxychloride leads to the by now very famihar conversion of the amide functions to enol chlorides (67-2). The displacement of halogen by hydrazine leads directly to the antihypertensive agent dihydralazine (67-3) [76]. 

Phthalazines were discovered as scaffolds for both PDE5 inhibitors and kinase inhibitors. Similarly, anthranilic acid amides were disclosed for both pharmacological activities (Figure 9.10). Compared to the phthalazines, putatively an internal H-bond keeps the two substituents in a comparable spatial arrangement. Extremely potent PDE5 inhibitors can be found in this class, e.g., 34 [40]. A similar internal H-bond can be speculated for 35, for which potent PDE5 inhibitory activity was likewise reported [41], Compound 36 represents the transition between phthalazines and anthranilic acid amides [42],... 

A rich coordination chemistry of aromatic diazine (N-N), especially pyridazine and phthalazine related ligands has emerged over the last three decades,1-72 and recently open-chain diazine (N-N) coordination chemistry has been well developed, especially by Thompson and others.62-113 Many types of aromatic heterocyclic compounds contain a 1,2-diazine (N-N) moiety, e.g., pyridazine and its 3,6-disubstituted derivatives (Scheme 1, Type 1), phthalazine, condensed phthalazines and their substituted derivatives (Scheme 1, Type 2), and other compounds such as pyrazole, triazole, thiadiazole, tetrazole, indazole, 1,2,4-triazine, 1,2,4,5-tetrazine, and thiadiazepines. Alternatively, the 1,2-diazine (N-N) moiety also exists as an open-chain entity in some related compounds, e.g., A-substituted-amide hydrazonimidates (Scheme 1, Type 3), A-substituted-amide hydrazonidates (Scheme 1, Type 4), A-substituted hydrazides (Scheme 1, Type 5), A-substituted amidrazones (Scheme 1, Type 6), and A-sub-stituted hydrazidates (Scheme 1, Type 7). 

As alternatives to the chloro compounds for substrates in nucleophilic displacement reactions, phenoxy compounds and cyclic amides and cyclic thioamides have been used. It appears that 2-phenoxyquinoxaline is significantly less reactive than the corresponding cinnoline or phthalazine derivatives and only gives a negligible yield of 2-aminoquinoxaline when heated with ammonium acetate. However the phenoxyquinoxaline 1 is converted in high yield into the aminoquinoxaline 2 on treatment with this reagent. ... 

But of prime importance with regard to the final separation process is the nature of the membrane-forming polymer its hydrophihdty, charge density, polymer structure and molecular weight Typical polymers used in this phase-separation process are cellulose esters (most commonly CA), polyamides, poly(amide-hydra-zides), polyimides, (sulfonated) polysulfones, poly(phenylene oxide) and (sulfona-ted) poly(phthalazine ether sulfone ketone). 

The Reissert compound, l-cyano-iV,A(-diethyl-l,2-dihydro-2-phthalazinecarbox-amide (126) with benzaldehyde in an alkaline medium gave l-(a-hydroxy-benzyl)phthalazine (128), allegedly via the intermediate (127) (PhCHO, NaOH, H2O, MeCN, PhCHjEtaNCl, 20°C, 2 h 15%). ... 

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